Skip to main content
SpringerLink
Log in

Zukunft des Aneuploidiescreenings

Priorität Diagnostik

The future of aneuploidy screening

Diagnosis first!

  • Leitthema
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Hintergrund

Die Schwangerschaftsraten nach In-vitro-Fertilisation (IVF) bzw. intrazytoplasmatischer Spermieninjektion (ICSI) liegen im Durchschnitt weltweit bei etwa 30 % pro Behandlungszyklus. Um die Erfolgschancen zu verbessern wurde das Präimplantationsscreening eingeführt. Dabei werden die häufigen, spontan auftretenden Chromosomenanomalien untersucht. Seit 2012 konnte erstmals in randomisierten kontrollierten Studien (RCTs) eine Verbesserung erzielt werden.

Fragestellungen

Welche Methoden werden angewendet? Wie sind die Ergebnisse? Was ist gesichert?

Methoden

Klinisch gibt es 5 Ziele: Steigerung der Erfolgsraten (Schwangerschaft, Implantation, Geburt), Senkung des Risikos für Mehrlinge, Aborte und Fehlbildungen sowie, „last but not least“, die Erkennung von absehbar niedrigen Erfolgsaussichten wegen einer hohen Aneuploidierate in den Eizellen. Anstelle eines eigentlichen Screenings werden auch Indikationen für ein Präimplantationsscreening vorgeschlagen, wie höheres Alter, erfolglose Embryotransfers, Fehlgeburten und starke Einschränkung des Spermiogramms. Biopsien werden an Eizellen, Zygoten, 8-Zellern und Blastozysten durchgeführt. Genetisch kommen v. a. Fluoreszenz-in-situ-Hybridisierung, quantitative Polymerasekettenreaktion (qPCR), Microarrays zum Einsatz, künftig wohl auch Next Generation Sequencing (NGS).

Ergebnisse

Die Chancen für Implantation und Geburt konnten gesteigert, die Risiken für Aborte und Mehrlinge gesenkt werden. Bei 40-jährigen Frauen hat eine von 4 Eizellen einen unauffälligen Chromosomensatz.

Diskussion

Das Präimplantationsscreening ist weiterhin experimentell, doch besteht nun eine große Wahrscheinlichkeit für den Nachweis klinischer Verbesserungen.

Schlussfolgerungen

Zunächst sollte die Methodik genutzt werden, um Frauen mit sehr niedrigen Chancen wegen hoher Eizellaneuploidieraten zu identifizieren. Diese sollten dann über eine Eizellspende aufgeklärt werden.

Abstract

Background

Pregnancy rates with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are on average approximately 30 % per treatment cycle globally. In order to improve the chances of success preimplantation genetic screening was introduced. Since 2012 some improvements could be demonstrated in randomized controlled trials (RCTs).

Objectives

Which methods were applied? What are the results? What seems to be the substantiated state of knowledge?

Methods

There are five clinical aims: increase of success rates (e.g. pregnancy, implantation and birth), decrease rates of miscarriages, multiples and malformations and last but not least the recognition of predictably very low chances because of high aneuploidy rates in oocytes. Instead of an actual screening approach, indications for testing have been proposed, such as advanced maternal age, repeated implantation failure, repeated miscarriages and strong reduction of spermiogram parameters. Biopsies were performed on oocytes, zygotes, 8-cell embryos and blastocysts. For genetic testing fluorescence in situ hybridization (FISH), quantitative polymerase chain reaction (qPCR), microarrays and next generation sequencing (NGS) were introduced.

Results

The chances for implantation, pregnancy and birth could be improved and the risks of miscarriages and multiples decreased. For women aged 40 years, one in four oocytes has a normal chromosome complement.

Discussion

Preimplantation genetic screening continues to be experimental; however, there is growing evidence to suggest a potential for clinical improvement.

Conclusions

Preimplantation genetic screening should initially be implemented to identify women with low chances of success because of high aneuploidy rates in oocytes. Oocyte donation is an option in these cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Bühler K, Balsch-Pratsch M, Blumenauer V et al (2012) DIR Annual 2011. J Reproduktionsmed Endokrinol 9:453–484

    Google Scholar 

  2. Chen W, Weimer J, Arnold N et al (2001) Molekularzytogenetische Untersuchung unbefruchteter menschlicher Eizellen, 1. Tagung des Arbeitskreises Molekularbiologie der Deutschen Gesellschaft für gynäkologische Endokrinologie und Fortpflanzungsmedizin (DGGEF), Düsseldorf 2001, Abstractband S. 5

  3. Forman EJ, Hong KH, Ferry KM et al (2013) In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 100:100–107

    Article  PubMed  Google Scholar 

  4. Geraedts J, Collins J, Gianaroli L et al (2010) What next for preimplantation genetic screening? A polar body approach! Hum Reprod 25:575–577

    Article  PubMed Central  PubMed  Google Scholar 

  5. Geraedts J (2011) ESHRE’s polar body array CGH trial now good to go. Focus Reprod 12

  6. Geraedts J, Montag M, Magli MC et al (2011) Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results. Hum Reprod 26:3173–3180

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Gianaroli L, Racowsky C, Geraedts J et al (2012) Best practices of ASRM and ESHRE: a journey through reproductive medicine. Fertil Steril 98(6):1380–1394

    Article  PubMed  Google Scholar 

  8. Griesinger G, Bündgen N, Salmen D et al (2009) Polar body biopsy in the diagnosis of monogenic diseases: the birth of three healthy children. Dtsch Arztebl Int 106(33):533–538

    PubMed Central  PubMed  Google Scholar 

  9. Handyside AH, Kontogianni EH, Hardy K, Winston RM (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344:768–770

    Article  CAS  PubMed  Google Scholar 

  10. Harper J, Coonen E, De Rycke M et al (2010) What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium Steering Committee. Hum Reprod 25(4):821–823

    Article  PubMed  Google Scholar 

  11. Harper JC, Wilton L, Traeger-Synodinos J et al (2012) The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update 18:234–247

    Article  CAS  PubMed  Google Scholar 

  12. Harton G, Braude P, Lashwood A et al (2011) ESHRE PGD consortium best practice guidelines for organization of a PGD centre for PGD/preimplantation genetic screening. Hum Reprod 26:14–24

    Article  CAS  PubMed  Google Scholar 

  13. Mastenbroek S, Twisk M, Veen F van der, Repping S (2011) Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 17(4):454–466

    Article  CAS  PubMed  Google Scholar 

  14. Munne S, Magli C, Cohen J et al (1999) Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 14:2191–2199

    Article  CAS  PubMed  Google Scholar 

  15. Munne S (2012) Preimplantation genetic diagnosis for aneuploidy and translocations using array comparative genomic hybridization. Curr Genomics 13(6):463–470

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Palermo G, Joris H, Devroey P, Van Steirteghem AC (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340(8810):17–18

    Article  CAS  PubMed  Google Scholar 

  17. Rubio C, Rodrigo L, Mir P et al (2013) Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results. Fertil Steril 99:1044–1048

    Article  CAS  PubMed  Google Scholar 

  18. Rubio C, Bellver J, Rodrigo L et al (2013) Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials. Fertil Steril 99:1400–1407

    Article  PubMed  Google Scholar 

  19. Schmutzler AG, Schmutzler RK, Krebs D, Gordon JW (1990) Polar body and blastomere biopsy in the mouse, Second Joint Meeting of the European Society of Human Reproduction and Embryology and the European Sterility Congress Organization, Milan, Italy. Human Reprod Programme and Abstracts, p. 7–8

  20. Schmutzler AG, Al-Hasani S, Diedrich K, Krebs D (1993) Geburt nach subzonaler Spermainjektion (SUZI) bei extremer männlicher Subfertilität. Geburtshilfe Frauenheilkd 53:854–856

    Article  CAS  PubMed  Google Scholar 

  21. Schmutzler A (2008) Praktische Ethik der Reproduktionsmedizin. In: Kaatsch HJ (Hrsg) Medizinethik. LIT, Münster

  22. Schmutzler AG, Acar-Perk B, Weimer J et al (2014) Sham-controlled implantation after preimplantation genetic screening by polar body biopsy and FISH. Arch Gynecol Obstet 289(2):439–444

    Article  PubMed  Google Scholar 

  23. Schoolcraft WB, Surrey E, Minjarez D et al (2012) Comprehensive chromosome screening (CCS) with vitrification results in improved clinical outcome in women > 35 years: a randomized control trial. Fertil Steril 98(3 Suppl):S1

    Article  Google Scholar 

  24. Scott RT Jr, Upham KM, Forman EJ et al (2013) Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril 100(3):697–703

    Article  PubMed  Google Scholar 

  25. Simpson JL (2012) Preimplantation genetic diagnosis to improve pregnancy outcomes in subfertility. Best Pract Res Clin Obstet Gynaecol 26:805–815

    Article  PubMed  Google Scholar 

  26. Tomi D, Griesinger G, Schultze-Mosgau A et al (2005) Polar body diagnosis for hemophilia a using multiplex PCR for linked polymorphic markers. J Histochem Cytochem 53(3):277–280

    Article  CAS  PubMed  Google Scholar 

  27. Tomi D, Schultze-Mosgau A, Eckhold J et al (2006) First pregnancy and life after preimplantation genetic diagnosis by polar body analysis for mucopolysaccharidosis type I. Reprod Biomed Online 12(2):215–220

    Article  PubMed  Google Scholar 

  28. Vanneste E, Voet T, Le Caignec C et al (2009) Chromosome instability is common in human cleavage-stage embryos. Nat Med 15(5):577–583

    Article  CAS  PubMed  Google Scholar 

  29. Verlinsky Y, Ginsberg N, Lifchez A et al (1990) Analysis of the first polar body: preconception genetic diagnosis. Hum Reprod 5:826–829

    CAS  PubMed  Google Scholar 

  30. Xu K, Montag M (2012) New perspectives on embryo biopsy: not how, but when and why? Semin Reprod Med 30:259–266

    Article  PubMed  Google Scholar 

  31. Yang Z, Liu J, Collins GS et al (2012) Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 5:24

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. A.G. Schmutzler. I. Filges, S. Al-Hasani, K. Diedrich und P. Miny geben an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Universitäts-Frauenklinik, Christian-Albrechts-Universität, UKSH, Campus Kiel, Arnold-Heller-Str. 3, Haus 24, 24105, Kiel, Deutschland

    A.G. Schmutzler

  2. Abteilung Medizinische Genetik, Universitätsspital, Universität Basel, Basel, Schweiz

    I. Filges & P. Miny

  3. Universitäts-Frauenklinik, Universität zu Lübeck, Lübeck, Deutschland

    S. Al-Hasani

  4. Facharzt-Zentrum für Kinderwunsch, pränatale Medizin, Endokrinologie und Osteologie, Amedes Experts, Hamburg, Deutschland

    K. Diedrich

Authors
  1. A.G. Schmutzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Filges
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Al-Hasani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Diedrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Miny
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A.G. Schmutzler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmutzler, A., Filges, I., Al-Hasani, S. et al. Zukunft des Aneuploidiescreenings. Gynäkologe 47, 263–270 (2014). https://doi.org/10.1007/s00129-013-3248-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00129-013-3248-1

Schlüsselwörter

Keywords

Search

Navigation